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Year : 2010  |  Volume : 2  |  Issue : 4  |  Page : 282-289 Table of Contents     

Introduction to metallic nanoparticles

1 Department of Pharmaceutical Sciences, Appalachian College of Pharmacy, 1060 Dragon Road, Oakwood, Virginia 246 14, USA
2 Department of Radiology, UT Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, Texas 753 90, USA
3 Department of Radiology, Dr. L.H. Hiranandani College of Pharmacy, Mumbai University, Ulhasnagar-421 003, India

Date of Submission21-Jun-2010
Date of Decision24-Jul-2010
Date of Acceptance28-Aug-2010
Date of Web Publication28-Oct-2010

Correspondence Address:
Vicky V Mody
Department of Pharmaceutical Sciences, Appalachian College of Pharmacy, 1060 Dragon Road, Oakwood, Virginia 246 14
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0975-7406.72127

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Metallic nanoparticles have fascinated scientist for over a century and are now heavily utilized in biomedical sciences and engineering. They are a focus of interest because of their huge potential in nanotechnology. Today these materials can be synthesized and modified with various chemical functional groups which allow them to be conjugated with antibodies, ligands, and drugs of interest and thus opening a wide range of potential applications in biotechnology, magnetic separation, and preconcentration of target analytes, targeted drug delivery, and vehicles for gene and drug delivery and more importantly diagnostic imaging. Moreover, various imaging modalities have been developed over the period of time such as MRI, CT, PET, ultrasound, SERS, and optical imaging as an aid to image various disease states. These imaging modalities differ in both techniques and instrumentation and more importantly require a contrast agent with unique physiochemical properties. This led to the invention of various nanoparticulated contrast agent such as magnetic nanoparticles (Fe 3 O 4 ), gold, and silver nanoparticles for their application in these imaging modalities. In addition, to use various imaging techniques in tandem newer multifunctional nanoshells and nanocages have been developed. Thus in this review article, we aim to provide an introduction to magnetic nanoparticles (Fe 3 O 4 ), gold nanoparticles, nanoshells and nanocages, and silver nanoparticles followed by their synthesis, physiochemical properties, and citing some recent applications in the diagnostic imaging and therapy of cancer.

Keywords: Fe 3 O 4 , gold nanoparticles, iron oxide nanoparticles, metallic nanoparticles, nanocages, nanoshells, silver nanoparticles

How to cite this article:
Mody VV, Siwale R, Singh A, Mody HR. Introduction to metallic nanoparticles. J Pharm Bioall Sci 2010;2:282-9

How to cite this URL:
Mody VV, Siwale R, Singh A, Mody HR. Introduction to metallic nanoparticles. J Pharm Bioall Sci [serial online] 2010 [cited 2022 Nov 30];2:282-9. Available from:

Nanotechnology refers to the branch of science and engineering dedicated to materials, having dimensions in the order of 100th of nm or less. [1] The term being new, but has been widely used for the development of more efficient technology. In recent years, nanotechnology has been embraced by industrial sectors due to its applications in the field of electronic storage systems, [2] biotechnology, [3] magnetic separation and preconcentration of target analytes, targeted drug delivery, [4],[5] and vehicles for gene and drug delivery. [2],[4],[5],[6] Consequently, with wide range of applications available, these particles have potential to make a significant impact to the society. Although new, the history of nanomaterials dates long back to 1959, when Richard P. Feynman, a physicist at Cal Tech, forecasted the advent of nanomaterials. In one of his class he said, "There is plenty of room at the bottom," and suggested that scaling down to nanolevel and starting from the bottom was the key to future technology and advancement. [6] As the field of nanotechnology advanced, novel nanomaterials become apparent having different properties as compared to their larger counterparts. This difference in the physiochemical properties of nanomaterials can be attributed to their high surface-to-volume ratio. Due to these unique properties, they make excellent candidate for biomedical applications as variety of biological processes occur at nanometer scales.

In general, nanoparticles used in the field of biotechnology range in particle size between 10 and 500 nm, seldom exceeding 700 nm. The nanosize of these particles allows various communications with biomolecules on the cell surfaces and within the cells in way that can be decoded and designated to various biochemical and physiochemical properties of these cells. [7] Similarly, its potential application in drug delivery system and noninvasive imaging offered various advantages over conventional pharmaceutical agents. [7] In an effort to utilize nanoparticles at their full throttle, it is important that the nanoparticulate systems should be stable, biocompatible, and selectively directed to specific sites in the body after systemic administration. More specific targeting systems are designed to recognize the targeted cells such as cancer cells. This can be achieved by conjugating the nanoparticle with an appropriate ligand, which has a specific binding activity with respect to the target cells. In addition, nanoparticles provide a platform to attach multiple copies of therapeutic substance on it and hence increase the concentration of therapeutic and diagnostic substances at the pathological site. Also, the concentration and dynamics of the active molecule can be varied by controlling the particle size of nanoparticles (>3-5 nm). This control in particle size in conjugation with surface coating with stealth ligand allows them to veil against body's immune system, enabling them to circulate in the blood for longer period of time. [7] These advances in the field of biotechnology have opened an endless opportunities for molecular diagnostics and therapy. [8] Once targeted (active or passive), these nanocarriers can be designed in a way to facilitate them to act as imaging probes using variety to techniques such as ultrasound (US), X-ray, computed tomography (CT), positron emission tomography (PET), magnetic resonance imaging (MRI), optical imaging, and surface-enhanced Raman imaging (SERS) [Table 1]. [9] Hence, these so-called "molecular imaging probes" can noninvasively provide valuable information about differentiate abnormalities in various body structures and organs to determine the extent of disease, and evaluate the effectiveness of treatment. [7] Thus short molecular imaging enables the visualization of the cellular function and the follow-up of the molecular process in living organisms without perturbing them. [10]
Table 1 :Comparison of common imaging techniques along with the nanoparticles currently used or under clinical trials[10]

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Over the year's nanoparticles such as magnetic nanoparticles (iron oxide), gold and silver nanoparticles, nanoshells, and nanocages have been continuously used and modified to enable their use as a diagnostic and therapeutic agent. Thus, in this particular review article we have introduced iron oxide, gold, and silver nanoparticles along with newer nanoshells and nanocages. These are then briefly discussed for their method of development and some citing recent examples which utilize their intrinsic properties as diagnostic and/or therapeutic agents for diseases, mainly cancer.

   Iron Oxide Nanoparticles Top

Iron (III) oxide (Fe 2 O 3 ) is a reddish brown, inorganic compound which is paramagnetic in nature and also one of the three main oxides of iron, while other two being FeO and Fe 3 O 4 . The Fe 3 O 4 , which also occurs naturally as the mineral magnetite, is also superparamagnetic in nature. Due to their ultrafine size, magnetic properties, and biocompatibility, superparamagnetic iron oxide nanoparticles (SPION) have emerged as promising candidates for various biomedical applications, such as enhanced resolution contrast agents for MRI, targeted drug delivery and imaging, hyperthermia, gene therapy, stem cell tracking, molecular/cellular tracking, magnetic separation technologies (e.g., rapid DNA sequencing) early detection of inflammatory, cancer, diabetes, and atherosclerosis. [11],[12],[13],[14],[15],[16],[17],[18],[19],[20] All these biomedical applications require that the nanoparticles have high magnetization values so as to provide high-resolution MR images. In general, the superparamagnetic nanoparticles resemble excellent imaging probes to be used as MRI contrast agents since the MR signal intensity is significantly modulated without any compromise in its in vivo stability. [21] Basically, all contrast agents induce a decrease in the T1 and T2 relaxation times of surrounding water protons and thereby manipulate the signal intensity of the imaged tissue. [22]

Converging advances in the understanding of the molecular biology of various diseases recommended the need of homogeneous and targeted imaging probes along with a narrow size distribution in between 10 and 250 nm in diameter. Developing magnetic nanoparticles in this diameter range is a complex process and various chemical routes for their synthesis have been proposed. These methods include microemulsions, sol−gel syntheses, sonochemical reactions, hydrothermal reactions, hydrolysis and thermolysis of precursors, flow injection syntheses, and electrospray syntheses. [23],[24],[25],[26],[27],[28],[29] However, the most common method for the production of magnetite nanoparticles is the chemical coprecipitation technique of iron salts. [30],[31],[32],[33],[34] The main advantage of the coprecipitation process is that a large amount of nanoparticles can be synthesized but with limited control on size distribution. This is mainly due to that the kinetic factors are controlling the growth of the crystal. Thus the particulate magnetic contrast agents synthesized using these methods include ultrasmall particles of iron oxide (USPIO) (10-40 nm), small particles of iron oxide (SPIO) (60-150 nm). Besides, monocrystalline USPIOs are also called as monocrystalline iron oxide nanoparticles (MIONs), whereas MIONs when cross-linked with dextran they are called crosslinked iron oxide nanoparticles CLIO (10-30 nm). [35],[36],[37] The modification of the dextran coating by carboxylation leads to a shorter clearance half-life in blood. [38] Hence, ferumoxytol (AMAG Pharmaceuticals), a carboxyalkylated polysaccharide coated iron oxide nanoparticle, is already described as a good first-pass contrast agent but uptake by macrophages is unspecific and too fast to enhance the uptake in macrophage-rich plaques.

In order to improve the cellular uptake, these particles can be modified with a peculiar surface coating so that they can be easily conjugated to drugs, proteins, enzymes, antibodies, or nucleotides and can be directed to an organ, tissue, or tumor [Figure 1]. [7],[39] While traditional contrast agents distribute rather nonspecifically, targeted molecular imaging probes based on iron oxide nanoparticles have been developed that specifically target body tissue or cells. [7],[40] For instance, Conroy and coworkers developed (chlorotoxin (CTX)) a biocompatible iron oxide nanoprobe coated with poly(ethylene glycol) (PEG), which is capable of specifically targeting glioma tumors via the surface-bound targeting peptide. [41] Further, MRI studies showed the preferential accumulation of the nanoprobe within gliomas. In another study, Apopa et al. engineered iron oxide nanoparticles that can induce an increase in cell permeability through the production of reactive oxygen species (ROS) and the stabilization of microtubules. [42] These are the few applications of iron oxide nanoparticles in biomedical imaging.
Figure 1 :Schematic diagram representing the fucntionalization of magnetic nanoparticles with bioresponsive peptide, PEG linker, chemotherapeutic agent, antibody, and cell-penetrating peptide.[11]

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These studies provide a new insight into the bioreactivity of engineered iron nanoparticles, which can provide potential applications in medical imaging or drug delivery. The further development and modification of the complexes of iron oxide along with dendrimers, polymeric nanoparticles, liposomes, and solid lipid nanoparticles are widely studied. However, the toxicity of these magnetic nanoparticles to certain types of neuronal cells is still the matter of concern. [43]

   Gold Nanoparticles Top

Colloidal gold, also known as gold nanoparticles, is a suspension (or colloid) of nanometer-sized particles of gold. The history of these colloidal solutions dates back to Roman times when they were used to stain glass for decorative purposes. [44] However, the modern scientific evaluation of colloidal gold did not begin until Michael Faraday's work of the 1850s, when he observed that the colloidal gold solutions have properties that differ from the bulk gold. [45],[46] Hence the colloidal solution is either an intense red color (for particles less than 100 nm) or a dirty yellowish color (for larger particles) as shown in [Figure 2] and [Figure 3]. [47],[48] These interesting optical properties of these gold nanoparticles are due to their unique interaction with light. [49] In the presence of the oscillating electromagnetic field of the light, the free electrons of the metal nanoparticles undergo an oscillation with respect to the metal lattice. [50],[51],[52],[53] This process is resonant at a particular frequency of the light and is termed the localized surface plasmon resonance (LSPR). After absorption, the surface plasmon decays radiatively resulting in light scattering or nonradiatively by converting the absorbed light into heat. Thus for gold nanospheres with particle size around 10 nm in diameter have a strong absorption maximum around 520 nm in aqueous solution due to their LSPR. These nanoshperes show a stokes shift with an increase in the nanosphere size due to the electromagnetic retardation in larger particles.
Figure 2 :Photographs of aqueous solutions of gold nanospheres (upper panels) and gold nanorods (lower panels) as a function of increasing dimensions. Corresponding transmission electron microscopy images of the nanoparticles are shown (all scale bars 100 nm). The difference in color of the particle solutions is more dramatic for rods than for spheres. This is due to the nature of plasmon bands (one for spheres and two for rods) that are more sensitive to size for rods compared with spheres. For spheres, the size varies from 4 to 40 nm (TEMs a-e), whereas for rods, the aspect ratio varies from 1.3 to 5 for short rods (TEMs f-j) and 20 (TEM k) for long rods[50]

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Figure 3 :Gold nanorods (NRs) with tunable optical absorptions at visible and near-infrared wavelengths; a) Optical absorption spectra of gold NRs with different aspect ratios (a-e); b) Color wheel, with reference to gold NRs labeled a-e. TR, transverse resonance[51]

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Moreover, the properties and applications of colloidal gold nanoparticles also depend upon its shape. [Figure 2] shows that the difference in color of the particle solutions is more dramatic for rods than for spheres. For example, the rod-shaped nanoparticles have two resonances: one due to plasmon oscillation along the nanorod short axis and another due to plasmon oscillation along the long axis, which depends strongly on the nanorod aspect ratio, that is, length-to-width ratio. [54],[55] When the nanorod aspect ratio is increased, the long-axis LSPR wavelength position red shifts from the visible to the NIR and also progressively increases in oscillator strength [Figure 2]. [55] For example, rodlike particles have both transverse and longitudinal absorption peak, and anisotropy of the shape affects their self-assembly. [56] Due to these unique optical properties, gold nanoparticles are the subject of substantial research, with enormous applications including biological imaging, electronics, and materials science. [57] Thus to develop gold nanoparticles for specific applications, reliable and high-yielding methods including those with spherical and nonspherical shapes have been developed over the period of years. [56],[58]

The most prevalent method for the synthesis of monodisperse spherical gold nanoparticles was pioneered by Turkevich et al. in 1951 and later refined by Frens et al. in 1973. [59],[60],[61],[62] This method uses the chemical reduction of gold salts such as hydrogen tetrachloroaurate (HAuCl 4 ) using citrate as the reducing agent. This method produces monodisperse spherical gold nanoparticles in the range of 10-20 nm in diameter. However, the synthesis of larger gold nanoparticles with diameters between 30 and 100 nm was reported by Brown and Natan via seeding of Au 3+ by hydroxylamine. [63] Subsequent research led to the modification of the shape of these gold nanoparticles resulting in rod, triangular, polygonal rods, and spherical particles. [64],[65],[66] These ensuing gold nanoparticles have unique properties, providing a high surface area to volume ratio. Moreover, the gold surface offers a unique opportunity to conjugate ligands such as oligonucleotides, proteins, and antibodies containing functional groups such as thiols, mercaptans, phosphines, and amines, which demonstrates a strong affinity for gold surface. [67] The realization of such gold nanoconjugates coupled with strongly enhanced LSPR gold nanoparticles have found applications in simpler but much powerful imaging techniques such as dark-field imaging, SERS, and optical imaging for the diagnosis of various disease states. [68]

In fact, El Sayed et al. have established the use of gold nanoparticles for cancer imaging by selectively transporting AuNPs into the cancer cell nucleus. In order to selectively transport the AuNPs into the cancer cell nucleus, they conjugated arginine−glycine−aspartic acid peptide (RGD) and a nuclear localization signal peptide (NLS) to a 30-nm AuNPs via PEG. [69] RGD is known to target αvβ6 integrins receptors on the surface of the cell, whereas NLS sequence lysine−lysine−lysine−arginine−lysine (KKKRK) sequence is known to associate with karyopherins (importins) in the cytoplasm, which enables the translocation to the nucleus. [70],[71],[72] Thus the presence of RGD will enable cancer-cell-specific targeting, whereas the presence of NLS will exhibit cancer cell nucleus specific targeting. This intuitively developed particle was then targeted to human oral squamous cell carcinoma (HSC) having αvβ6 integrins overexpressed on the cell surface (cancer model), and human keratinocytes (HaCat) (control). The authors further demonstrated that RGD-AuNPs specifically target the cytoplasm of cancer cells [Figure 4]a over that of normal cells [Figure 4]c, and the RGD/NLS-AuNPs specifically target the nuclei of cancer cells [Figure 4]b over those of normal cells [Figure 4]d. [69]
Figure 4 :Dark field light scattering images of cytoplasm and nuclear targeting AuNPs. a) RGD-AuNPs located in the cytoplasm of cancer cells. b) RGD/NLS-AuNPs located at the nucleus of cancer cells. c) RGD-AuNPs located in the cytoplasm of normal cells. d) RGD/NLS-AuNPs located at the nucleus of normal cells. The cancer and normal cells were incubated in the presence of these AuNPs at a concentration of 0.4 nM for 24 hours and these images clearly display the efficient uptake of AuNPs in cancer cells compared with normal cells. Scale bar 10 μm[72]

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Similarly, Qian et al. reported the development of tumor-targeted gold nanoparticles as a probe for Raman scatters in vivo. [73] These gold nanoparticles were encoded with a Raman reporter and further encapsulated with a thiol-modified PEG coat. Additionally, to specifically target tumor cells, the pegylated gold nanoparticles were then conjugated with an antibody against epidermal growth factor receptor, which is sometimes overexpressed in certain types of cancer cells. The Raman enhancement from these tailored particles was then observed with electronic transitions at 633 or 785 nm via SERS. The results obtained by Qian and coworkers suggest the highly specific recognition and detection of human cancer cells, as well as active targeting of EGFR-positive tumor xenografts in animal models can be made using SERS. [73]

Moreover, the use of gold nanorods as photothermal agents sets them apart from all nanoprobes. Photothermal therapy (PTT) is a procedure in which a photosensitizer is excited with specific band light (mainly IR). This activation brings the sensitizer to an excited state where it then releases vibrational energy in the form of heat. The heat is the actual method of therapy that kills the targeted cells. One of the biggest recent successes in photothermal therapy is the use of gold nanoparticles. Spherical gold nanoparticles absorptions have not been optimal for in vivo applications. This is because the peak absorptions have been limited to 520 nm for 10 nm diameter. Moreover, skin, tissues, and hemoglobin have a transmission window from 650 up to 900 nm. This was circumvented by the recent invention of gold nanorods by Murphy and Coworkers, who were able to tune the absorption peak of these nanoparticles, which can also be tuned from 550 nm up to 1 ΅m just by altering its aspect ratio of the nanorods [Figure 3]. [48],[74] Hence, for the rod-shaped gold nanoparticles with the absorption in the IR region, when selectively accumulated in tumors when bathed in laser light (in the IR region), the surrounding tissue is barely warmed, but the nanorods convert light to heat, killing the malignant cells. This potential application of gold nanorods sanctifies them from other nanoprobes. However, their incompatibility with other high-resolution imaging techniques such as MRI and irreproducibility in shapes led to the invention of nanocages and nanoshells.

   Nanoshells and Nanocages Top

Neeves and Birnboim calculated that a composite spherical particle consisting of a metallic shell and a dielectric core could give rise to LSPR modes with their wavelengths tunable over a broad range of the electromagnetic spectrum. [75] Later on, the experimental and theoretical work by Naomi Halas and Peter Nordlander at Rice University showed that the resonance of a silica-gold nanoshell particle can easily be positioned in the near-infrared (800-1,300 nm) region, where absorption by biomatters is low [Figure 5]. [76],[77],[78] They developed silica-gold nanospheres by using freshly formed amine-terminated silica spheres. These amine terminated silica spheres were then treated with a suspension of gold colloids (1-2 nm in size). Gold was deposited via chemical reduction to cover the silica core and to the amine terminal of the silicon core. Although this method is widely used, the intricacy involved in the control of thickness and smoothness of the metallic shells makes this method unsuitable for the routine synthesis of controlled particle-sized nanoshells. Furthermore, they also showed the successful irreversible photothermal ablation of tumor tissue both in vitro and in vivo when these nanoshells were localized onto the tumor cells. In another study, Halas and West established the use of near-infrared resonant nanoshells for whole-blood immunoassays. They further showed that the nanoshells when conjugated with antibodies act as recognition sites for a specific analyte [Figure 6]. The analyte causes the formation of dimmers, which will modify the LSPR. [79] Subsequent work in this field led to the development of the multifunctional magnetic gold nanoshells (Mag-GNS) by Jaeyun et al. utilizing Fe 3 O 4 nanoparticles as the magnetic core. The Fe 3 O 4 nanoparticles allow MRI for diagnosis, and the gold nanoshells enable photothermal therapy. By attaching an antibody to the Mag-GNS by a PEG linker, cancer cells can be targeted. Once localized, these particles enable the detection of cancer using MRI, whereas the photothermal therapy can be used to get rid of cancer cells. [80]
Figure 5 :G old nanoshell plasmon resonances for a 120-nm core with indicated shell thickness[81]

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Figure 6 :Formation of nanoshell dimer with the interaction of antibodies immobilized on the surface of the nanoshells[82]

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Similar to gold nanoshells, gold nanocages represent a novel class of nanostructures that are hollow porous gold nanoparticles that absorb light in the near-infrared range. They were first developed by the Xia and Coworkers via the reaction of silver nanoparticles with chloroauric acid (HAuCI 4 ) in boiling water. [81] Their LSPR peaks can also be tuned to the near infrared region by controlling the thickness and porosity of the walls. Comparable to nanoshells they have found applications in drug delivery and/or controlled drug release. Furthermore, the hollow interiors can host small objects such as magnetic nanoparticles to construct multifunctional hybrid nanostructures diagnostic imaging and therapy.

   Silver Nanoparticles Top

Silver nanoparticles are the particles of silver, with particle size between 1 and 100 nm in size. While frequently described as being "silver" some are composed of a large percentage of silver oxide due to their large ratio of surface to bulk silver atoms. Like gold nanoparticles, ionic silver has a long history and was initially used to stain the glass for yellow. Currently, there is also an effort to incorporate silver nanoparticles into a wide range of medical devices, including bone cement, surgical instruments, surgical masks, etc. Moreover, it has also been shown that ionic silver, in the right quantities, is suitable in treating wounds. [82],[83],[84] In fact, silver nanoparticles are now replacing silver sulfadiazine as an effective agent in the treatment of wounds. Additionally, Samsung has created and marketed a material called Silver Nano, which includes silver nanoparticles on the surfaces of household appliances. Moreover, due to their attractive physiochemical properties these nanomaterials have received considerable attention in biomedical imaging using SERS. In fact, the surface plasmon resonance and large effective scattering cross-section of individual silver nanoparticles make them ideal candidates for molecular labeling. [85] Thus many targeted silver oxide nanoprobes are currently being developed.

Typically, they are synthesized by the reduction of a silver salt with a reducing agent like sodium borohydride in the presence of a colloidal stabilizer. The most common colloidal stabilizers used are polyvinyl alcohol, poly(vinylpyrrolidone), bovine serum albumin (BSA), citrate, and cellulose. Newer novel methods include the use of ί-d-glucose as a reducing sugar and a starch as the stabilizer to develop silver nanoparticles ion implantation used to create silver nanoparticles. [86] Also, it is important to note that not all nanoparticles created are equal. The size and shape have been shown to have an impact on its efficacy. In fact, Elechiguerra et al. demonstrated that silver nanoparticles undergo a size-dependent interaction with HIV-1, with particles exclusively in the range of 1-10 nm attached to the virus. [87] They further suggest that silver nanoparticles interact with the HIV-1 virus via preferential binding to the gp120 glycoprotein knobs. [87] Similarly, Furno and Coworkers have developed biomaterials by impregnating silicone coated with silver oxide nanoparticles using supercritical carbon dioxide. [88] These novel biomaterials were developed with an aim to reduce the antibacterial infection. The results obtained were mixed but the methodology allows for the first-time silver impregnation (as opposed to coating) of medical polymers and promises to lead to an antimicrobial biomaterial. [88]

Even though these particles are not as widely preferred as compared to the gold nanoparticles and nanoshells, but they have made a tremendous impact on today's era of medical science. The interesting property of the noble metals is a promise that they would be continuously used as newer applications and protocols are being developed.

   Conclusion Top

This review article provides a glimpse to some simpler nanoparticles which are being currently modified for their potential applications in medicine. However, the field of nanoscience has blossomed over the last two decades and the need for nanotechnology to explore beyond the cells walls has become more important. [89] Nanoparticles have successfully come to aid various disease states, but the advances in biomedical imaging depend largely on the shape, size, and selectivity of the nanoparticle to the target. [89] Moreover, the type of the particle synthesized also governs the imaging modality to be used and thus the cost of diagnosis. Even though current investigations have demonstrated that multivalent composite materials can provide significant advantages, the ambiguity in developing them for a particular target with high specificity is still challenging. Fortunately, the field of nanotechnology continues to grow interest within the chemical research community with major discoveries as well as new scientific challenges. [44] Nevertheless, the future studies should also aim to address safety and biocompatibility of these nanoparticles, in particular long-term toxicities. [90] Additional clinical studies on humans and on animal models should be performed to substantiate their use especially in biomedical imaging using MRI, CT, ultrasound, PET, SERS, and optical imaging. [90]

   References Top

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  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6]

  [Table 1]

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53 Application of Nanoparticles and Melatonin for Cryopreservation of Gametes and Embryos
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54 Recent Advances in Metal-Based Antimicrobial Coatings for High-Touch Surfaces
Martin Birkett, Lynn Dover, Cecil Cherian Lukose, Abdul Wasy Zia, Murtaza M. Tambuwala, Ángel Serrano-Aroca
International Journal of Molecular Sciences. 2022; 23(3): 1162
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55 Nanoparticles Loaded with Platinum Drugs for Colorectal Cancer Therapy
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International Journal of Molecular Sciences. 2022; 23(19): 11261
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56 Phytochemicals Mediated Synthesis of AuNPs from Citrullus colocynthis and Their Characterization
Bismillah Mubeen, Mahvish Ghulam Rasool, Inam Ullah, Rabia Rasool, Syed Sarim Imam, Sultan Alshehri, Mohammed M. Ghoneim, Sami I. Alzarea, Muhammad Shahid Nadeem, Imran Kazmi
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57 Synthesis and Characterization of Silver Nanoparticles from Rhizophora apiculata and Studies on Their Wound Healing, Antioxidant, Anti-Inflammatory, and Cytotoxic Activity
Saeed Ali Alsareii, Abdulrahman Manaa Alamri, Mansour Yousef AlAsmari, Mohammed A. Bawahab, Mater H. Mahnashi, Ibrahim Ahmed Shaikh, Arun K. Shettar, Joy H. Hoskeri, Vijay Kumbar
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58 Biostimulation of Anaerobic Digestion Using Iron Oxide Nanoparticles (IONPs) for Increasing Biogas Production from Cattle Manure
Dilbag Singh, Kamla Malik, Meena Sindhu, Nisha Kumari, Vijaya Rani, Shikha Mehta, Karmal Malik, Poonam Ranga, Kashish Sharma, Neeru Dhull, Shweta Malik, Nisha Arya
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59 Applications of Various Types of Nanomaterials for the Treatment of Neurological Disorders
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60 Inorganic Nanomaterials in Tissue Engineering
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61 Green Synthesis of Silver Nanoparticles Using Bellevalia Flexuosa Leaves Extract
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62 Liver-specific drug delivery platforms: Applications for the treatment of alcohol-associated liver disease
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63 Recent Advancements in Plant-Derived Nanomaterials Research for Biomedical Applications
Rashmi Trivedi, Tarun Kumar Upadhyay, Mohd Hasan Mujahid, Fahad Khan, Pratibha Pandey, Amit Baran Sharangi, Khursheed Muzammil, Nazim Nasir, Atiq Hassan, Nadiyah M. Alabdallah, Sadaf Anwar, Samra Siddiqui, Mohd Saeed
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64 Plasmonic Nanoparticles as Optical Sensing Probes for the Detection of Alzheimer’s Disease
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65 Simple Equations Pertaining to the Particle Number and Surface Area of Metallic, Polymeric, Lipidic and Vesicular Nanocarriers
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67 Effect of Saffron Extract on the Hepatotoxicity Induced by Copper Nanoparticles in Male Mice
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68 Toward a Better Understanding of Metal Nanoparticles, a Novel Strategy from Eucalyptus Plants
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69 The Evaluation of Drug Delivery Nanocarrier Development and Pharmacological Briefing for Metabolic-Associated Fatty Liver Disease (MAFLD): An Update
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70 Emerging Applications of Nanotechnology in Healthcare Systems: Grand Challenges and Perspectives
Sumaira Anjum, Sara Ishaque, Hijab Fatima, Wajiha Farooq, Christophe Hano, Bilal Haider Abbasi, Iram Anjum
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71 Nanocarrier-Mediated Topical Insulin Delivery for Wound Healing
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72 Electroactive Polymeric Composites to Mimic the Electromechanical Properties of Myocardium in Cardiac Tissue Repair
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73 Discovery, Optimization, and Clinical Application of Natural Antimicrobial Peptides
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74 Do Lipid-based Nanoparticles Hold Promise for Advancing the Clinical Translation of Anticancer Alkaloids?
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75 Nanoantibiotics: Functions and Properties at the Nanoscale to Combat Antibiotic Resistance
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76 Mechanisms of Macrophage Plasticity in the Tumor Environment: Manipulating Activation State to Improve Outcomes
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77 Emerging Concern for Silver Nanoparticle Resistance in Acinetobacter baumannii and Other Bacteria
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78 External and Internal Stimuli-Responsive Metallic Nanotherapeutics for Enhanced Anticancer Therapy
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79 Recapitulation of Cancer Nanotherapeutics
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80 Therapeutic Potential of Green Synthesized Metallic Nanoparticles Against Staphylococcus aureus
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81 Effect of graphene / metal nanocomposites on the key genes involved in rosmarinic acid biosynthesis pathway and its accumulation in Melissa officinalis
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82 Nanotechnology approaches for delivery and targeting of Amphotericin B in fungal and parasitic diseases
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83 Near-infrared Light and Metallic Nanoparticles
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84 Nanotechnology and Animal Health
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85 Magnetic Properties of Fe, Co and Ni Based Nanopowders Produced by Chemical-Metallurgy Method
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86 Eco friendly synthesis and characterization of zinc oxide nanoparticles from Aegle marmelos and its cytotoxicity effects on MCF-7 cell lines
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87 Green synthesis of silver nanoparticles using Omani pomegranate peel extract and two polyphenolic natural products: characterization and comparison of their antioxidant, antibacterial, and cytotoxic activities
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88 Recent Advancement in Topical Nanocarriers for the Treatment of Psoriasis
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89 Novel Eco-Friendly Synthesis of Biosilver Nanoparticles as a Colorimetric Probe for Highly Selective Detection of Fe (III) Ions in Aqueous Solution
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90 Molecular Dynamics Simulation of the Coalescence and Melting Process of Cu and Ag Nanoparticles
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91 Recent progress and applications of gold nanotechnology in medical biophysics using artificial intelligence and mathematical modeling
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92 Nanoparticles and Nanomotors Modified by Nucleic Acids Aptamers for Targeted Drug Delivery
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93 Metallic nanoparticles as drug delivery system for the treatment of cancer
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94 Curcumin as a novel reducing and stabilizing agent for the green synthesis of metallic nanoparticles
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95 Performance of copper oxide nanoparticles treated polyaniline-itaconic acid based magnetic sensitive polymeric nanocomposites for the removal of chromium ion from industrial wastewater
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96 Optical and Morphology Properties of the Magnetite ( Fe3O4) Nanoparticles Prepared by Green Method
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97 Biogenic synthesis of Pd-nanoparticles using Areca Nut Husk Extract: a greener approach to access a-keto imides and stilbenes
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98 Nanoencapsulation of Plant Volatile Organic Compounds to Improve Their Biological Activities
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99 Preparation of silver and gold nanoparticles by the pinhole DC plasma system
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100 Nanomaterials for bioprinting: functionalization of tissue-specific bioinks
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101 CS/Au/MWCNT nanohybrid as an efficient carrier for the sustained release of 5-FU and a study of its cytotoxicity on MCF-7
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102 Effect of gold nanoparticle treated dorsal root ganglion cells on peripheral neurite differentiation
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103 A method based on asymmetric flow field flow fractionation hyphenated to inductively coupled plasma mass spectrometry for the monitoring of platinum nanoparticles in water samples
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104 Development of a Structural Comparison Method to Promote Exploration of the Potential Energy Surface in the Global Optimization of Nanoclusters
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105 Cu–Ag Alloy Nanoparticles in Hydrogel Nanofibers for the Catalytic Reduction of Organic Compounds
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106 Nanotechnology and Plant Viruses: An Emerging Disease Management Approach for Resistant Pathogens
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107 Low-dimensional nanomaterials enabled autoimmune disease treatments: Recent advances, strategies, and future challenges
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108 Nanomaterials: Types, properties, synthesis, emerging materials, and toxicity concerns
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109 Design of lipid-based nanocarrier for drug delivery has a double therapy for six common pathogens eradication
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110 Challenges and strategies for in situ endothelialization and long-term lumen patency of vascular grafts
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111 Investigation of the effect of nanoparticles on platelet storage duration 2010–2020
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112 Application of strontium-based nanoparticles in medicine and environmental sciences
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113 Positive and negative effects of nanoparticles on agricultural crops
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114 The physiological and biochemical responses to engineered green graphene/metal nanocomposites in Stevia rebaudiana
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115 Advances in Thiopurine Drug Delivery: The Current State-of-the-Art
Ahmed B. Bayoumy, Femke Crouwel, Nripen Chanda, Timothy H. J. Florin, Hans J. C. Buiter, Chris J. J. Mulder, Nanne K. H. de Boer
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116 Nanomaterials for chronic inflammatory diseases: the current status and future prospects
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117 Dual-reductant synthesis of nickel nanoparticles for use in screen-printing conductive paste
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118 Electrochemical Detection of Ascorbic acid in Orange on Iron(III) Oxide Nanoparticles Modified Screen Printed Carbon Electrode
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119 Modification of the Mechanical Properties of Core-Shell Liquid Gallium Nanoparticles by Thermal Oxidation at Low Temperature
Sergio Catalán-Gómez, Andrés Redondo-Cubero, Miguel Morales, María de la Mata, Sergio I. Molina, Francisco J. Palomares, Alberto Carnicero, Jose L. Pau, Luis Vázquez
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120 Embracing nanomaterials' interactions with the innate immune system
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121 A path toward the clinical translation of nano-based imaging contrast agents
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122 Nanocarrier-delivered small interfering RNA for chemoresistant ovarian cancer therapy
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123 Nanomedicine: Photo-activated nanostructured titanium dioxide, as a promising anticancer agent
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124 Clinical therapies and nano drug delivery systems for urinary bladder cancer
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125 Nanoarchitectonics is an emerging drug/gene delivery and targeting strategy -a critical review
Vivekanandhan Karthik, Shanmugam Poornima, Arumugam Vigneshwaran, Daniel Paul Raj Dharun Daniel Raj, Ramasamy Subbaiya, Sivasubramanian Manikandan, Muthupandian Saravanan
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126 Effect of temperature on green synthesized silver nanoparticles using water and methonol
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127 Biogenic synthesis of metallic nanoparticles: Principles and applications
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128 Efficiency of cerium oxide (CeO2) nano-catalyst in degrading the toxic and persistent 4-nitrophenol in aqueous solution
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129 Nanodelivery of natural isothiocyanates as a cancer therapeutic
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130 Recent update of toxicity aspects of nanoparticulate systems for drug delivery
Soma Patnaik, Bapi Gorain, Santwana Padhi, Hira Choudhury, Gamal A. Gabr, Shadab Md, Dinesh Kumar Mishra, Prashant Kesharwani
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131 Improving temozolomide biopharmaceutical properties in glioblastoma multiforme (GBM) treatment using GBM-targeting nanocarriers
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132 Accumulation and cellular toxicity of engineered metallic nanoparticle in freshwater microalgae: Current status and future challenges
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133 Nanomedicines accessible in the market for clinical interventions
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134 Cyclodextrins-modified metallic nanoparticles for effective cancer therapy
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135 Evaluation of magnesium oxide and zinc oxide nanoparticles against multi-drug-resistance Mycobacterium tuberculosis
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136 Impact of metal nanoparticles on the structure and function of metabolic enzymes
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137 Nanotechnology as a promising platform for rheumatoid arthritis management: Diagnosis, treatment, and treatment monitoring
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138 The uses of resveratrol for neurological diseases treatment and insights for nanotechnology based-drug delivery systems
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139 Nanoarchitectronics: A versatile tool for deciphering nanoparticle interaction with cellular proteins, nucleic acids and phospholipids at biological interfaces
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140 Big impact of nanoparticles: analysis of the most cited nanopharmaceuticals and nanonutraceuticals research
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141 Highly stable AgNPs prepared via a novel green approach for catalytic and photocatalytic removal of biological and non-biological pollutants
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142 Colorimetric detection of Gadidae species using probe-modified gold nanoparticles
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143 Nanoparticles: Synthesis, characteristics, and applications in analytical and other sciences
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144 Selection of resistance by antimicrobial coatings in the healthcare setting
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145 Biomedical and photocatalytic applications of biosynthesized silver nanoparticles: Ecotoxicology study of brilliant green dye and its mechanistic degradation pathways
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146 Enhancement the electrical conductivity of the synthesized polyvinylidene fluoride/polyvinyl chloride composite doped with palladium nanoparticles via laser ablation
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147 Magnetic, fluorescent and hybrid nanoparticles: From synthesis to application in biosystems
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148 Synthesis and characterization of cecropin peptide-based silver nanocomposites: Its antibacterial activity and mode of action
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149 Nanocarriers for effective nutraceutical delivery to the brain
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150 Ropinirole silver nanocomposite attenuates neurodegeneration in the transgenic Drosophila melanogaster model of Parkinson's disease
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151 The challenge of using nanotherapy during pregnancy: Technological aspects and biomedical implications
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152 Synthesis of Metal Nanostructures Using Supercritical Carbon Dioxide: A Green and Upscalable Process
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153 Potential Applications of Advanced Nano/Hydrogels in Biomedicine: Static, Dynamic, Multi-Stage, and Bioinspired
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154 Antimicrobial Metal Nanomaterials: From Passive to Stimuli-Activated Applications
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155 Label-free Immunosensor for the Determination of Microcystin-LR in Water
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156 Electrochemical Determination of Caffeine Using Bimetallic Au-Ag Nanoparticles Obtained from Low-cost Green Synthesis
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157 Structural, Morphological and Biological Features of ZnO Nanoparticles Using Hyphaene thebaica (L.) Mart. Fruits
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158 Nanodelivery of phytobioactive compounds for treating aging-associated disorders
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159 Influence of PVP polymer concentration on nonlinear absorption in silver nanoparticles at resonant excitation
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160 First principle study of silver nanoparticle interactions with antimalarial drugs extracted from Artemisia annua plant
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161 Synthesis, characterization and biocompatibility studies of carbon quantum dots from Phoenix dactylifera
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162 Recent advances in understanding oligonucleotide aptamers and their applications as therapeutic agents
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163 Laser ablation of Ni in the presence of external magnetic field: Selection of microsized particles
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164 A study of magnetic, antibacterial and antifungal behaviour of a novel gold anchor of polyaniline/itaconic acid/Fe3O4 hybrid nanocomposite: Synthesis and characterization
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165 Revising the dark fermentative H2 research and development scenario – An overview of the recent advances and emerging technological approaches
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166 Nano-based delivery systems for berberine: A modern anti-cancer herbal medicine
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167 Molecular dynamics simulation of size, temperature, heating and cooling rates on structural formation of Ag-Cu-Ni ternary nanoparticles (Ag34-Cu33-Ni33)
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168 Metal-Based Nanostructures/PLGA Nanocomposites: Antimicrobial Activity, Cytotoxicity, and Their Biomedical Applications
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169 Properties of a-Brass Nanoparticles. 1. Neural Network Potential Energy Surface
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170 Water safety screening via multiplex LAMP-Au-nanoprobe integrated approach
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171 Influence of nanoparticles on liver tissue and hepatic functions: A review
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172 Citrate-silver nanoparticles and their impact on some environmental beneficial fungi
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173 Porous organic polymer material supported palladium nanoparticles
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174 Nanotechnology-based drug delivery systems for enhanced diagnosis and therapy of oral cancer
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175 Nanotheranostic agents for neurodegenerative diseases
Terry Tetley, Jorge Bernardino de la Serna, Sonia Antoranz Contera, Parasuraman Padmanabhan, Mathangi Palanivel, Ajay Kumar, Domokos Máthé, George K. Radda, Kah-Leong Lim, Balázs Gulyás
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176 Integrated analytical platforms for the comprehensive characterization of bioconjugated inorganic nanomaterials aiming at biological applications
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177 Structural and optical studies of silver sulfide nanoparticles from silver(I) dithiocarbamate complex: molecular structure of ethylphenyl dithiocarbamato silver(I)
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179 Characterization and antibacterial of Gold Nanoparticles Prepared by Electrolysis method
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180 Biosynthesis, antimicrobial spectra and applications of silver nanoparticles: current progress and future prospects
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181 Microbial contamination and plaque scores of nanogold-coated toothbrush
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182 The Effects of Polymer Coating of Gold Nanoparticles on Oxidative Stress and DNA Damage
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183 Nanomaterial integration into the scaffolding materials for nerve tissue engineering: a review
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184 Metalik nanopartiküllerin hedeflendirilmesi
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185 Atherosclerosis and Nanomedicine Potential: Current Advances and Future Opportunities
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186 Trends in Nanomedicines for Cancer Treatment
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187 The Use of Montmorillonite (MMT) in Food Nanocomposites: Methods of Incorporation, Characterization of MMT/Polymer Nanocomposites and Main Consequences in the Properties
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188 Nanocarriers(s) Based Approaches in Cancer Therapeutics
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189 Nanobulges: A Duplex Nanosystem for Multidimensional Applications
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190 An Overview of Strategic Non-Biological Approaches for The Synthesis of Cupper Nanoparticles
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191 Changes in the microbiocenosis of the rumen and digestibility of the dry matter of the diet with the introduction of gobies together fatty addition of ultrafine iron particles
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192 Nanodelivery of Natural Antioxidants: An Anti-aging Perspective
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193 Injectable Hydrogel-Based Nanocomposites for Cardiovascular Diseases
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194 Nanoapproaches to Modifying Epigenetics of Epithelial Mesenchymal Transition for Treatment of Pulmonary Fibrosis
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195 Nanoparticles as Potential Antivirals in Agriculture
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196 Creating Structured Hydrogel Microenvironments for Regulating Stem Cell Differentiation
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197 Advances in Ultrasonic Spray Pyrolysis Processing of Noble Metal Nanoparticles—Review
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198 Optimized Polyethylene Glycolylated Polymer–Lipid Hybrid Nanoparticles as a Potential Breast Cancer Treatment
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199 Current Research of Graphene-Based Nanocomposites and Their Application for Supercapacitors
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200 Green Synthesis of Silver Nanoparticles Using Astragalus tribuloides Delile. Root Extract: Characterization, Antioxidant, Antibacterial, and Anti-Inflammatory Activities
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201 Intranasal Delivery of Nanoformulations: A Potential Way of Treatment for Neurological Disorders
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202 Antifungal and Cytotoxic Evaluation of Photochemically Synthesized Heparin-Coated Gold and Silver Nanoparticles
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203 Green Synthesis of Fe2O3 Nanoparticles from Orange Peel Extract and a Study of Its Antibacterial Activity
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204 Prodrugs in combination with nanocarriers as a strategy for promoting antitumoral efficiency
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205 Greener synthesis of ZnO and Ag–ZnO nanoparticles using Silybum marianum for diverse biomedical applications
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206 Glycan Carriers As Glycotools for Medicinal Chemistry Applications
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207 Anticancer activity of green synthesised gold nanoparticles from Marsdenia tenacissima inhibits A549 cell proliferation through the apoptotic pathway
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208 Plasmon-Induced Dimerization of Thiazolidine-2,4-dione on Silver Nanoparticles: Revealed by Surface-Enhanced Raman Scattering Study
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209 Effect of Phosphate, Sulfate, Arsenate, and Pyrite on Surface Transformations and Chemical Retention of Gold Nanoparticles (Au–NPs) in Partially Saturated Soil Columns
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210 Effect of Substrates on Catalytic Activity of Biogenic Palladium Nanoparticles in C–C Cross-Coupling Reactions
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211 Progress in neuromodulation of the brain: A role for magnetic nanoparticles?
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212 Colourimetric detection of swine-specific DNA for halal authentication using gold nanoparticles
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213 Microfluidically Assisted Construction of Hierarchical Multicomponent Microparticles for Short Intermediate Diffusion Paths in Heterogeneous Catalysis
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214 Amplification of resonance Rayleigh scattering of gold nanoparticles by tweaking into nanowires: Bio-sensing of a-tocopherol by enhanced resonance Rayleigh scattering of curcumin capped gold nanowires through non-covalent interaction
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215 Nanoparticle-Based Immunochemical Biosensors and Assays: Recent Advances and Challenges
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216 Anticancer activity of metal nanoparticles and their peptide conjugates against human colon adenorectal carcinoma cells
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217 Novel nanoparticulate systems for lung cancer therapy: an updated review
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218 Lyotropic liquid crystal-assisted synthesis of micro- and nanoparticles of silver
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219 Green synthesis, characterisation and bioactivity of plant-mediated silver nanoparticles using Decalepis hamiltonii root extract
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220 Enhanced anticancer effect of copper-loaded chitosan nanoparticles against osteosarcoma
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221 Effects of pulsed laser irradiation on gold-coated silver nanoplates and their antibacterial activity
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222 Antibacterial Activities of Silver Nanoplates Controlled by Pulsed Laser
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223 Therapeutic targeting in nanomedicine: the future lies in recombinant antibodies
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224 Metal-Based Nanoparticles for the Treatment of Infectious Diseases
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225 Heterogeneous Vascular Bed Responses to Pulmonary Titanium Dioxide Nanoparticle Exposure
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226 Recent progress in theranostic applications of hybrid gold nanoparticles
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227 Fabrication of adenosine 5'-triphosphate-capped silver nanoparticles: Enhanced cytotoxicity efficacy and targeting effect against tumor cells
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228 Nano-therapeutics: A revolution in infection control in post antibiotic era
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229 Nanoparticle-mediated drug delivery system for atherosclerotic cardiovascular disease
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230 Actinomycetes mediated synthesis of gold nanoparticles from the culture supernatant of Streptomyces griseoruber with special reference to catalytic activity
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231 Green synthesis of silver nanoparticles using Azadirachta indica leaf extract and its antimicrobial study
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232 Anthelmintic effects of zinc oxide and iron oxide nanoparticles against Toxocara vitulorum
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234 Biogenic synthesis of Marsilea quadrifolia gold nanoparticles: a study of improved glucose utilization efficiency on 3T3-L1 adipocytes
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235 Iron and iron oxide nanoparticles are highly toxic to Culex quinquefasciatus with little non-target effects on larvivorous fishes
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236 Implementation of nanoparticles in therapeutic radiation oncology
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239 Green Synthesis of Silver Nanoparticles: A Review
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240 Green Synthesis of Smart Metal/Polymer Nanocomposite Particles and Their Tuneable Catalytic Activities
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241 Cryo-electron microscopy and cryo-electron tomography of nanoparticles
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